C-kit expression in sarcomatoid renal cell carcinoma: potential therapy with imatinib

J Urol. 2004 Jun;171(6 Pt 1):2176-80. doi: 10.1097/01.ju.0000127727.33232.cf.

Abstract

Purpose: Sarcomatoid (S) renal cell carcinoma (RCC) is an uncommon subtype of RCC with a poor prognosis because of its local aggressiveness and high metastatic rate. Currently, there is no specific, effective treatment for it. A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. We investigated c-Kit expression in this type of tumor, which to our knowledge has not been previously described.

Materials and methods: We reviewed 215 cases of RCC diagnosed at our department from 1995 to 2002. Of the cases 20 (9.3%) were SRCC. Formalin fixed, paraffin embedded material was available in 19 cases. We performed immunohistochemical staining against c-Kit using rabbit polyclonal antihuman antibody (CD117, Dako Corp., Carpinteria, California), diluted 1:100. Its expression was evaluated in the epithelial and the spindle components.

Results: Two of the 20 SRCC cases (10%) showed no epithelial differentiation. The epithelial component was conventional RCC in 10 cases (50%), papillary RCC in 5 (25%) and chromophobe RCC in 3 (15%). A total of 16 cases (80%) presented at an advanced stage at diagnosis, namely T3 or T4 and/or metastatic disease. Immunohistochemical study showed positivity in the epithelial component only in the 3 chromophobe SRCCs. The sarcomatoid component was positive for c-Kit in 18 cases (94.7%).

Conclusions: High c-Kit expression in SRCC in our series and the existence of a target therapy, imatinib (STI-571), against cells that express this receptor open the possibility of using this treatment for these tumors, especially in cases of advanced disease.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Imatinib Mesylate
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / therapeutic use*
  • Sarcoma / genetics

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit